Jump to main content
Jump to site search

Issue 3, 2014
Previous Article Next Article

Poly(lactic acid) nanoparticles of the lead anticancer ruthenium compound KP1019 and its surfactant-mediated activation

Author affiliations

Abstract

Nanoparticle formulations offer besides the advantage of passive drug targeting also the opportunity to increase the stability of drugs. KP1019 is a lead ruthenium(III) compound which has been successfully tested in a clinical phase I trial. However, it is characterized by low stability in aqueous solution especially at physiological pH. To overcome this limitation, poly(lactic acid) (PLA) nanoparticles of KP1019 with two different surfactants (Pluronic F68 and Tween 80) were prepared by a single oil-in-water (o/w) emulsion. Cytotoxicity measurements comparing different aged Tween 80 nanoparticles revealed that the color change from brown to green was associated with an up to 20 fold increased activity compared to “free” KP1019. Further investigations suggested that this is based on the formation of enhanced intracellular reactive oxygen species levels. Additional studies revealed that the origin of the green color is a reaction between KP1019 and Tween 80. Kinetic studies of this reaction mixture using UV-Vis, ESI-MS and ESR spectroscopy indicated on the one hand a coordination of Tween 80 to KP1019, and on the other hand, the color change was found to correlate with a reduction of the Ru(III) center by the surfactant. Together, the results provide a first experimental approach to stabilize a biologically active Ru(II) species of KP1019 in aqueous solution, which probably can be also used to selectively generate this activated species in the tumor tissue via delivery of KP1019 using Tween 80 nanoparticles.

Graphical abstract: Poly(lactic acid) nanoparticles of the lead anticancer ruthenium compound KP1019 and its surfactant-mediated activation

Back to tab navigation

Publication details

The article was received on 29 Aug 2013, accepted on 10 Oct 2013 and first published on 11 Oct 2013


Article type: Paper
DOI: 10.1039/C3DT52388H
Citation: Dalton Trans., 2014,43, 1096-1104
  • Open access: Creative Commons BY license
  •   Request permissions

    Poly(lactic acid) nanoparticles of the lead anticancer ruthenium compound KP1019 and its surfactant-mediated activation

    B. Fischer, P. Heffeter, K. Kryeziu, L. Gille, S. M. Meier, W. Berger, C. R. Kowol and B. K. Keppler, Dalton Trans., 2014, 43, 1096
    DOI: 10.1039/C3DT52388H

    This article is licensed under a Creative Commons Attribution 3.0 Unported Licence. Material from this article can be used in other publications provided that the correct acknowledgement is given with the reproduced material.

    Reproduced material should be attributed as follows:

    • For reproduction of material from NJC:
      [Original citation] - Published by The Royal Society of Chemistry (RSC) on behalf of the Centre National de la Recherche Scientifique (CNRS) and the RSC.
    • For reproduction of material from PCCP:
      [Original citation] - Published by the PCCP Owner Societies.
    • For reproduction of material from PPS:
      [Original citation] - Published by The Royal Society of Chemistry (RSC) on behalf of the European Society for Photobiology, the European Photochemistry Association, and RSC.
    • For reproduction of material from all other RSC journals:
      [Original citation] - Published by The Royal Society of Chemistry.

    Information about reproducing material from RSC articles with different licences is available on our Permission Requests page.

Search articles by author

Spotlight

Advertisements